Tert-butyl 2-(3-hydroxypropyl)piperidine-1-carboxylate → 3-(5-Bromo-2-fluorobenzyloxy)-1-[1-(t-butoxycarbonyl)piperidin-2-yl]propane

Temperature

-40 °C

3-[1-(t-Butoxycarbonyl)piperidin-2-yl]propanol (800 mg, 3.29 mmol) was taken up in tetrahydrofuran (17 ml), cooled to −40° C., and treated with potassium t-butoxide (1 M in tetrahydrofuran, 3.62 ml, 3.62 mmol). The resulting mixture was stirred at −40° C. for about 35 minutes, then cooled to −78° C. To this mixture was then added 5-bromo-2-fluorobenzyl bromide (881 mg, 3.29 mmol) as a solution in tetrahydrofuran (5 ml). The resultant yellow reaction mixture was slowly warmed to 0° C. and stirred for about four hours. The reaction mixture was diluted with methylene chloride and washed with 1 M potassium carbonate and brine. The organic fraction was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude oil was purified by high performance liquid chromatography, yielding 707 mg (50%) of the title intermediate as a clear oil.

1. temperaturecooled to −78° C
2. temperatureThe resultant yellow reaction mixture was slowly warmed to 0° C.
3. stirringstirred for about four hours
4. washwashed with 1 M potassium carbonate and brine
5. dry with materialThe organic fraction was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude oil was purified by high performance liquid chromatography

ORD record

ord-7614dc538d59408793cd7e31cecb893b

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06245761B1